TY - JOUR
T1 - Role of CD45 signaling pathway in galactoxylomannan-induced T cell damage
AU - Pericolini, Eva
AU - Gabrielli, Elena
AU - Bistoni, Giovanni
AU - Cenci, Elio
AU - Perito, Stefano
AU - Chow, Siu Kei
AU - Riuzzi, Francesca
AU - Donato, Rosario
AU - Casadevall, Arturo
AU - Vecchiarelli, Anna
PY - 2010
Y1 - 2010
N2 - Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45-/- cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45-/- cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis.
AB - Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45-/- cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45-/- cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis.
UR - http://www.scopus.com/inward/record.url?scp=77958588490&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958588490&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0012720
DO - 10.1371/journal.pone.0012720
M3 - Article
C2 - 20856869
AN - SCOPUS:77958588490
SN - 1932-6203
VL - 5
SP - 1
EP - 13
JO - PloS one
JF - PloS one
IS - 9
M1 - e12720
ER -